PROCESS MAPPING

OF
INSULIN PRODUCTS
INDENT PROCEDURE

Novo nordisk
placed Production
Production
demand Collect Collect
details of last of last
details Enter available
plan prepared
plan prepared
issued batch
issued batch stock as on date
AT INDRAD
AT INDRAD
BANGLORE when indent
● calculate material requirement
●
● calculate
calculate material
batch requirement
●
● complete batch
calculate batch manufacturing process
● complete batch manufacturing process
● dispatch batch
● dispatch batch

Entire details
Place
Place require
require snap
snap
should entered in
off cap
off cap
separate formate

● make crystal requirement

● make crystal requirement
● also make requirement
Make fax indent Send fax to ● also make requirement for
for meta cresol, glycerol, phenol
copy Bangalore
banglore metacresol, glycerol, phenol crystal
crystal
● ask expiry date of m cresol
● ask expiry date of m cresol

TOTAL TIME- 3 HOUR

GENERAL INFORMATION :

INSULIN PRODUCTS

• Location : TPL INDRAD

• Production in TPL since 1990

Product Range : Insulin A

Insulin B
Insulin C
Insulin D
• Market : Domestic

• Weekly off : Sunday ( normally 15 days production continuously run to increase productivity)
-- 2 Sundays are off in a month. e.g- 1 & 3, 2 & 4

• Packing : 1 shift ( 12 hrs basis)

• Schedule-H : is effective for domestic products

• RM/ PM testing : TPL INDRAD

• SFG Testing : TPL INDRAD

-- 1 batch sent to Novo Nordisk from 10 batches

 PRODUCTION METHOD
• Production is generally done through Batch manufacturing.
• Batch manufacturing is divided into two parts.
o Day 1 manufacturing
o Day 2 manufacturing
• BATCH SIZE – 80,000 vial
• Vials are made up of molded glass & its content of drug is- 10 ml

 PRECAUSION
• Insulin is very “HEAT SENSITIVE” so its products are treated with special care while production
• STERILIZATION is done through filtration method using membrane filter.
• Insulin products are stored in cold temperature at 2-8°C.
PROCESS FLOW

PPC (1 DAYS)
Monthly Production plan is FORMULATION
prepared Weekly Manufacturing PO (Product order) release in PPC
plan is prepared

MRN (Material requisition note) release after PO

1. Primary packing material from PM store
2. Raw material from RM store

Empty vial inspection

Batch manufacturing (3 DAYS)
• Mixing
• Filling
• Sealing
• Collection
Snap off cap inspection
Washing and sterilization

Cold room storage

Products store at 2-8 ºC

Q C Inspection (15 DAYS)

Final release by
QA/QC

Product Packing (2 DAYS)

BSR (2 DAYS)
(Bonded Storage Room)

Final Dispatch (2 DAYS)

TOTAL LEAD TIME = 25 DAYS

 PARALLEL PROCESSES

• Empty vial inspection

• Snap off cap washing & sterilization

PRODUCTION & PACKING CAPACITY:

• Production: 22- 26 batches / 1 month
• Packing capacity : 60,000 / 12 hr
• Vial washing/ filing / sealing : 100-120 vial / 1 minute
• Snap off cap washing : 15,000 / 90 minute

6.0 CONCLUSION:

• The Aseptic process simulation study clearly indicates that the exact time an Insulin product can
last is 39 hrs. 58 min (Approx. 40 hrs.) of holding after filtration + 20hrs. of filling.
• The process simulation test of vial filling and sealing line with SCD media filling confirmed that
aseptic condition is maintained throughout the formulation and filling process with reported
interventions.
• The purpose of the exercise is to simulate the condition of Day-1 and Day-2 preparation of
suspension products like INSULIN C, Insulin D and, INSULIN B holding during the weekly holiday
and commencing the filling operation on next day (After holiday) found acceptable.

The products can be manufactured before weekly holiday, which can be filled on next working day
after holiday

SO, MASTER PRODUCTION SCHEDULE IS EXCELLENT.

INJECTION PROCEDURE

Manufacturing Vial washing & drying Filling Q.C

3 DAYS 14 DAYS
2
DAYS

Bonded storage room Packaging

Packing
(BSR) quantity

3 DAYS

TOTAL LEAD TIME= 22 DAYS

EARLIER PROCESS

MANUFACTURING
Q.C PACKAGING MORE LEAD
TIME

CURRENT PROCESS

Q.C DECREASE
LEAD TIME
MANUFACTURING (22 DAYS)

PACKAGING
Batch size: 80,000 vials (800 Ltrs)
Products:
Insulin A (√) 10 ml
Insulin B (√) 10 ml
Insulin C (√) 10 ml
Insulin D (√) 10 ml
(*(√) main products)

Total Production: 25-26 Batches

Suggestion: Continue production monthly to increase 2-3 batches
Constraint: Manpower
Shift changes with 15 days so employee need 1 day off during shift change.
Production is continuing running 24 hrs per day.
Employee is continuing working 15 days.

MATRICS: MANUFACTURING PROCESS LEAD TIME vs RATED CAPACITY PROJECT:

LEAD TIME
ACTIVITY RATED CAPACITY
(Batch time)
13-15 hrs
Snap off cap inspection
6200 vials/hr
Washing and sterilization
(80,000 vials)
15 hr
Aseptic Filling & Sealing 6000 vials/hr

4 Ltrs / minute 4-4.5 hr.

Sterilization
(400 vials) (800 Lts)

(5000 vials/8 hr) *

Visual Inspection 96 hrs
one employee

Equipment table:
 Capacit
Equipm Capacity Capacity @
Sr. Capacity y@1
Equipment Name ent Area @ 2 shift 3 shift per
No per hour shift
Code per day day
per day
Vial wash machine 6200
49600 99200
1 WS-03 Washing 1488 vials
vials vials
(Klenzaid) (10 ml) vials/hr
Vial wash machine (semi 1100
8800 17600
2 WS-04 26400 vials
vials vials
auto) (5 ml) vials/hr
Cap wash machine (semi 1500 cap/
8000
3 WS-05 16000 cap 24000 cap
cap
auto) (5 ml) 90 minutes
Ampoule wash machine 1600-
200-300 3200- 4800-7200
4 WS-06 2400
vials/hr 4800 vials vials
No. 1 vials
Ampoule wash machine
6200 49600 99200
5 WS-07 1488 vials
vials/hr vials vials
No. 3
Ampoule wash machine
1100 8800 17600
6 WS-08 26400 vials
vials/hr vials vials
No. 4
Ampoule wash machine
1500 cap/ 8000
7 WS-09 16000 cap 24000 cap
90 minutes cap
No. 5
Vial filling machine
6000 48000 96000 144000
8 FL-01 filling
vials/hr vials vials vials
(Klenzaid) (10 ml)
Vial filling machine (semi
4968
9 FL-02 621 vials/hr 9936 vials 14904 vials
vials
auto) (5 ml)
4 head ampoule filing 1600-
200- 3200- 4800-7200
10 FL-07 2400
300amp/hr 4800 vials vials
machine No.1 (Cadmach) vials
1600-
4 head ampoule filing 200- 3200- 4800-7200
11 FL-08 2400
machine No.2 (Cadmach) 300amp/hr 4800 vials vials
vials
1600-
4 head ampoule filing 200- 3200- 4800-7200
12 FL-09 2400
machine No.3 (Cadmach) 300amp/hr 4800 vials vials
vials
Vial sealing machine
6000
13 SL-01 Sealing
vials/hr
(Klenzaid) (10ml)
Vila Sealing machine (semi
14 621 vials/hr
auto)
15 Vial sterling tunnel ST-01 Sterilizat 350º C 10 60 min 120 min 180 min
 ion
(Kleinzaid) min 40 sec

185º C 450
16 Dry Heat Sterilizer ST-02
min 1 tank
121º C 40
17 Autoclave No. 2 (Ventilator) ST-04
min
Regular Steam sterilizer
18 S-06
No.2
 PROCESS MAPPING
OF
EXHIBIT PROCEDURE

EXHIBIT

• Exhibit is Regulatory terminology.

• It is related to supplement. (Prefix/Suffix)
• Products which are in exhibit they can’t sell in market so they are for only education purpose and
submission only.
• Main Aim of Exhibit is conversion of development scale to commercial scale.
• Develop at TRC (Torrent Research Centre) with minimum quantity for registration for develop and exhibit.

Process Flow:
 TRC PPC
Formulation Department
(Torrent Research centre) Scheduling of mfg/packing
of Exhibit batches as per
rolling plan
Formulation
RM/PM indenting for
exhibit batches
Chemical test and Physical
analytical test Packing plan

Fix the formulation

Approval from FDA

(Foreign Drug Authority)

• Minimum 1 Lack Units require for the manufacturing of exhibit batches.

EBA (Exhibit Batch Area) AREA:

Equipment Table: (Room Temperature: 24-25 ºC and RH (Humidity): 29-32 %)

Equipment Equipment Equipment

Sr. No Room
code name capacity
1 GR-59 PLM (Planetary Mixer) 40 liters
2 GR-60 Pam Glatt 125 liters
3 FN-55 GR-64 Stirrer 80 liters
4 (Granulation GR-62 RMG (Rapid Mixer Granulator) 170 liters
5 Area) GR-61 RMG (Rapid Mixer Granulator) 73 liters
6 OG (Oscillating Granulator)
7 ML (Communicating Mill)
 FN-75
8 (Compression TC-61 Compression machine
Area)
9 FN-58 TC-62 Compression machine
10 TC-59 Metal Detector
11 TC-64 Tippler
12 TC-63 Tippler
13 TC-65 Detectors
FN-59
14 FC-08 Tablet coating Machine
(Coating Area)
15 ML-22 Colloidal Mill
16 FN-52 GR-58 Blender
FN-53
17 (Inspection IN-55 Pam Inspection machine
Area)

Compression Area:
1. Compression machine speed:

SR. No Machine Type of tooling Tablet Size No of stations

1 TC-61- (cadmac) D-tooling Large 26
2 TC-62 (cadmac) B-tooling Small 32

RPM Speed: 25, 30, 35, 40, 60, 70

Coating Area:

Coating Type:
o 2 spray and 3 spray

Coating Machine pan: 24, 34, 36

 EBA – Production process flow

Raw material dispensing (24 hour)

Shifting and milling (1 hour)

Granulation
Glatt (3 hour)
FBP (30 min)
(Fluid Bed Processor)

Sizing (1 hour)

Blending (30 min)

Compression (3 hour)

Coating (6 hour)

SAP sample Q.A. / Q.C.

Inspection (3 hour) Batch release

Packing

TOTAL HOUR = 42 HOUR

 Documentation work flow in EBA

MFC prepared in TRC BMR (Batch Material Record)

(Torrent Research Centre) prepared in production
(Master Formulae Card) Department

Sampling protocol prepared

Pilot summary
production Department
(Exhibit batch
Parameters to be monitored
summary)

Process Protocol

Process validation BMR

3 Validation batches prepared

YES

Validation summary
Process parameter fixed

BMR final for commercial

IMPORTANT POINTS FOR EXHIBIT BATCHES

√ Exhibit batches are prepared only on small scale, for trial purpose only.

√ Only tablet are formulated in EBA (Exhibit batch area). Capsules & injections are not
prepared.

√ Minimum 1 lakh unit containing batches are prepared in EBA.

√ Here EBA has only formulation department.

√ All Exhibit batches are not fixed shift wise because aim of EBA is to complete batches only,

because these are for regulatory submission only considered a scale up batch.